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Previous studies show that advanced liver fibrosis in long-term viral infections is linked to higher rates of antiviral treatment failures. Additionally, treatment failure is associated with high quasispecies fitness, which indicates greater viral diversity and adaptability. As a result, resistant variants may emerge, reducing retreatment effectiveness and increasing the chances of viral relapse. Additionally, using a mutagenic agent in monotherapy can accelerate virus evolution towards a flat-like quasispecies structure. This study examines 19 chronic HCV patients who failed direct-acting antiviral (DAA) treatments, using NGS to analyze quasispecies structure in relation to fibrosis as a marker of infection duration. Results show that HCV evolves towards a flat-like quasispecies structure over time, leading also to advanced liver damage (fibrosis F3 and F4\/cirrhosis). Based on our findings and previous research, we propose that the flat-like fitness quasispecies structure is the final stage of any quasispecies in chronic infections unless eradicated. The longer the infection persists, the lower the chances of achieving a cure. Interestingly, this finding may also be applicable to other chronic infection and drug resistance in cancer.<\/jats:p>","DOI":"10.3390\/microorganisms12112213","type":"journal-article","created":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T04:59:54Z","timestamp":1730437194000},"page":"2213","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Association of Liver Damage and Quasispecies Maturity in Chronic HCV Patients: The Fate of a Quasispecies"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4253-8015","authenticated-orcid":false,"given":"Josep","family":"Gregori","sequence":"first","affiliation":[{"name":"Liver Diseases-Viral Hepatitis, Liver Unit, Vall d\u2019Hebron Institut of Research (VHIR), Vall d\u2019Hebron Barcelona Hospital Campus, Passeig Vall d\u2019Hebron 119-129, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3428-2168","authenticated-orcid":false,"given":"Marta","family":"Iba\u00f1ez-Lligo\u00f1a","sequence":"additional","affiliation":[{"name":"Liver Diseases-Viral Hepatitis, Liver Unit, Vall d\u2019Hebron Institut of Research (VHIR), Vall d\u2019Hebron Barcelona Hospital Campus, Passeig Vall d\u2019Hebron 119-129, 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain"},{"name":"Medicine Department, Universitat Aut\u00f2noma de Barcelona (UAB), Campus de la UAB, Placa C\u00edvica, 08193 Bellaterra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergi","family":"Colomer-Castell","sequence":"additional","affiliation":[{"name":"Liver Diseases-Viral Hepatitis, Liver Unit, Vall d\u2019Hebron Institut of Research (VHIR), Vall d\u2019Hebron Barcelona Hospital Campus, Passeig Vall d\u2019Hebron 119-129, 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain"},{"name":"Biochemistry and Molecular Biology Department, Universitat Aut\u00f2noma de Barcelona (UAB), Campus de la UAB, Placa C\u00edvica, 08193 Bellaterra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0132-7027","authenticated-orcid":false,"given":"Carolina","family":"Campos","sequence":"additional","affiliation":[{"name":"Liver Diseases-Viral Hepatitis, Liver Unit, Vall d\u2019Hebron Institut of Research (VHIR), Vall d\u2019Hebron Barcelona Hospital Campus, Passeig Vall d\u2019Hebron 119-129, 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain"},{"name":"Biochemistry and Molecular Biology Department, Universitat Aut\u00f2noma de Barcelona (UAB), Campus de la UAB, Placa C\u00edvica, 08193 Bellaterra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0009-038X","authenticated-orcid":false,"given":"Damir","family":"Garc\u00eda-Cehic","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0014-084X","authenticated-orcid":false,"given":"Josep","family":"Quer","sequence":"additional","affiliation":[{"name":"Liver Diseases-Viral Hepatitis, Liver Unit, Vall d\u2019Hebron Institut of Research (VHIR), Vall d\u2019Hebron Barcelona Hospital Campus, Passeig Vall d\u2019Hebron 119-129, 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain"},{"name":"Medicine Department, Universitat Aut\u00f2noma de Barcelona (UAB), Campus de la UAB, Placa C\u00edvica, 08193 Bellaterra, Spain"},{"name":"Biochemistry and Molecular Biology Department, Universitat Aut\u00f2noma de Barcelona (UAB), Campus de la UAB, Placa C\u00edvica, 08193 Bellaterra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gallego, I., Eugenia Soria, M., Garc\u00eda-Crespo, C., Chen, Q., Mart\u00ednez-Barrag\u00e1n, P., Khalfaoui, S., Mart\u00ednez-Gonz\u00e1lez, B., Sanchez-Martin, I., Palacios-Blanco, I., and de \u00c1vila, A.I. (2020). Broad and Dynamic Diversification of Infectious Hepatitis C Virus in a Cell Culture Environment. J. 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